The effect of repetitive action potentials in the postsynaptic axon on the release of synaptic transmitter from the presynaptic terminal was investigated at the squid giant synapse. Repetitive antidromic stimulation of the postsynaptic axon resulted in a reduction in EPSP amplitude. The reduction in transmitter release was accompanied by a decrease in the presynaptic spike after-hyperpolarization (AH). Increasing the concentration of extracellular potassium ions also reduced the EPSP and decreased the amplitude of the presynaptic spike AH. The reduction in transmitter release resulting from repetitive postsynaptic impulses is attributed to the accumulation of extracellular potassium ions. The accumulation of extracellular potassion ions may thus modulate synaptic transmission and function as an integrative mechanism in the nervous system.